Childhood-onset Obsessive-compulsive disorder (OCD) and tic disorders appear to arise, in some cases, as sequelae of common childhood infections, including Group A beta-hemolytic streptococcal (GABHS) infections. Children whose symptoms begin or exacerbate following GABHS infections may belong to a subgroup of neuropsychiatric disorders identified by the acronym PANDAS (for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The subgroup shares several common clinical characteristics and may share a common pathophysiology for their symptoms. Investigations of the nature and treatment of this novel subgroup are ongoing. During this reporting period, additional experience has been gained in the use of long-term antibiotic administration (prophylaxis) to prevent post-streptococcal neuropsychiatric symptom exacerbations. A paper comparing the prophylactic efficacy of azithromycin and penicillin was published this year, and a pilot placebo-controlled investigation of penicillin prophylaxis was conducted at two sites: the NIMH IRP and the University of Florida - Gainesville. In addition, the sites are collaborating on an examination of the relationship between symptom onset and clinical course. Children with recent-onset OCD are enrolled in the trial and followed prospectively for up to two years to determine whether or not acute, dramatic onset of symptoms will predict an episodic course. Further, associations between symptom exacerbation and streptococcal infections are being tracked to determine whether or not membership in the PANDAS subgroup can be predicted at initial presentation. An ongoing collaboration with Drs. Madeleine Cunningham (Univ. Oklahoma) and Christina Kirvan (UC-Davis) is examining the relationship between cross-reactive antineuronal antibodies and symptoms in the PANDAS subgroup. Replication of preliminary results is nearing completion and will be reported when results are confirmed.